Gastric secretion of acid, chloride and pepsin and gastrin release, as well as pulse and blood pressure, are being studied in conscious dogs with Komarov esophagostomy and gastric cannula. Stimuli are given in dose response experiments using various histamine analogs (agonists and antagonists), alone or in combination with other stimuli such as gastrin (or bonbesin which releases endogenous gastrin) or urecholine. The relative effects on different H-2 sensitive systems (acid, pepsin, heart rate, blood pressure) are compared and related to drug structure, Gastric secretion using pentagastrin dose responses and sham-feeding as well as gastrin release using food and bombesing are being studied in patients with D.U., G.U. and in controls. These results are related to each other and to clinical data on age, sex, duration of disease, family history, incidence of complications and where applicable results of vagotomy. In those with very high BAO a circulating secretagogue is being sought, using a sensitive rat bioassay. Pepsinogen secretion is being studied in isolated pepsin glands from the esophagus of Rana catesbeiana. The optimum conditions of stimulation by cholinergics, the substrate requirements, relation of secretion to metabolism and to protein synthesis is to be studied.